REVIEW: Immunology of Apoptosis and Necrosis

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S. Ya. Proskuryakov^1*, V. L. Gabai², A. G. Konoplyannikov¹, I. A. Zamulaeva¹, and A. I. Kolesnikova¹

¹Medical Radiological Research Center, Russian Academy of Medical Sciences, ul. Koroleva 4, 249036 Obninsk, Russia; fax: (7-095) 965-1440; E-mail: pros@mrrc.obninsk.ru

²Department of Biochemistry, K-323, Boston University School of Medicine, 715 Albany St., Boston MA 02118, USA; fax: 617-638-5339

^* To whom correspondence should be addressed.

Received October 18, 2004; Revision received February 16, 2005

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A complex of reactions regulating the number of cells in organs and tissues under normal and pathologic conditions is one of the most important systems of multicellular organisms. In this system, which controls both cell proliferation and clearance, clearance has been given special attention during the last three decades. Some stages of the clearance are known (the choice of “unwanted” cells, their destruction not affecting the surrounding tissue, and, finally, removal of the corpses), and undeniable progress has been achieved in the understanding of the second stage mechanisms, whereas mechanisms of elimination per se of cells or their fragments still continue to be terra incognita. The clearance of such cells is mainly determined by different components of natural and adaptive immunity: phagocytes, complement, opsonins, antigen-presenting cells, etc. Recently specific “danger signals”, such as hydrolases, DNA, heat shock proteins, and other potential immunogens released by cells during their elimination have been discovered. Entering the extracellular space, these signals induce inflammation and injury of the surrounding tissues, i.e., autoimmune reactions. Heat shock proteins, in addition to chaperon activity, act as signaling, costimulating, and antigen-carrying molecules in the interactions of dying cells and the immune system.

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KEY WORDS: programmed clearance of apoptotic and necrotic cells, immune system, danger signals, heat shock proteins

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